Gonzaga Natália Almeida, Batistela Melissa Resende, Padovan Diego, de Martinis Bruno Spinosa, Tirapelli Carlos Renato, Padovan Cláudia Maria
Laboratório de Neurobiologia do Estresse e da Depressão, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Cidade Universitária, 14040-901 Ribeirão Preto, SP, Brazil; Programa de Pós-graduação em Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Cidade Universitária, 14040-900, Ribeirão Preto SP, Brazil.
Laboratório de Neurobiologia do Estresse e da Depressão, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Cidade Universitária, 14040-901 Ribeirão Preto, SP, Brazil.
Alcohol. 2016 May;52:1-8. doi: 10.1016/j.alcohol.2016.02.001. Epub 2016 Feb 26.
Nitric oxide (NO) mediated transmission in the dorsal raphe nucleus (DRN) has been shown to be involved in the modulation of anxiety-like behaviors. We investigated whether inhibition of nitric oxide synthase (NOS) in the DRN would prevent anxiety-like behavior induced by ethanol withdrawal. Male Wistar rats were treated with ethanol 2-6% (v/v) for a period of 21 days. Ethanol withdrawal was induced by abrupt discontinuation of the treatment. Experiments were performed 48 h after ethanol discontinuation. Rats with a guide cannula aimed at the DRN received intra-DRN injections of the non-selective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME), selective neuronal NOS (nNOS) inhibitor N(ω)-propyl-l-arginine (NPLA), or selective inhibitor of inducible NOS (iNOS) N-([3-(aminomethyl)phenyl] methyl) ethanimidamidedihydrochloride (1400W). Five minutes later, the animals were tested in the elevated plus maze (EPM). Plasma ethanol levels were determined by gas chromatography. There was a reduction in plasma ethanol levels 48 h after ethanol withdrawal. Rats from the ethanol withdrawal group showed decreased exploration of the open arms of the EPM with no change in the exploration of enclosed arms. Intra-DRN treatment with l-NAME (100 nmoles/0.2 μL) and 1400W (1 nmol/0.2 μL), but not NPLA (10 nmoles/0.2 μL) in the DRN attenuated the decrease in the exploration of the open arms of the EPM induced by ethanol withdrawal. The major new finding of the present study is that iNOS in the DRN plays a role in the anxiety-like behavior induced by ethanol withdrawal.
一氧化氮（NO）介导的中缝背核（DRN）中的神经传递已被证明参与了焦虑样行为的调节。我们研究了抑制DRN中的一氧化氮合酶（NOS）是否能预防乙醇戒断诱导的焦虑样行为。雄性Wistar大鼠用2-6%（v/v）的乙醇处理21天。通过突然停止处理诱导乙醇戒断。在乙醇戒断后48小时进行实验。将带有导向套管并瞄准DRN的大鼠进行DRN内注射非选择性NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）、选择性神经元NOS（nNOS）抑制剂N（ω）-丙基-L-精氨酸（NPLA）或诱导型NOS（iNOS）的选择性抑制剂N-([3-(氨基甲基)苯基]甲基)乙亚胺二盐酸盐（1400W）。五分钟后，在高架十字迷宫（EPM）中对动物进行测试。通过气相色谱法测定血浆乙醇水平。乙醇戒断后48小时血浆乙醇水平降低。乙醇戒断组的大鼠对EPM开放臂的探索减少，而对封闭臂的探索没有变化。在DRN中用L-NAME（100纳摩尔/0.2微升）和1400W（1纳摩尔/0.2微升）进行DRN内处理，但不是用NPLA（10纳摩尔/0.2微升），可减轻乙醇戒断诱导的EPM开放臂探索减少。本研究的主要新发现是DRN中的iNOS在乙醇戒断诱导的焦虑样行为中起作用。
